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To investigate the feasibility of percutaneous radiofrequency (RF) ablation to occlude the thoracic duct (TD) in a swine model with imaging and histologic correlation.Six swine underwent TD RF ablation. Two terminal (4 hours, 1 open and 1 percutaneous) and 4 survival (30 days, all percutaneous) studies were performed. Two 20-gauge needles were placed adjacent to the TD under direct visualization after right thoracotomy or under fluoroscopic guidance using a percutaneous transabdominal approach after intranodal lymphangiography. RF electrodes were advanced through the needles, and ablation was performed at 90°C for 90 seconds. Lymphangiography was performed, and the TD and adjacent structures were resected and examined microscopically at the end of each study period.Four of 6 subjects survived the planned study period and underwent follow-up lymphangiography. Two subjects in the survival group were euthanized early-1 after developing an acute chylothorax and 1 because of gastric volvulus 14 days after ablation. Occlusion of the targeted TD segment was noted on lymphangiography in 3 of the 4 remaining subjects (2 acute and 1 survival). Histology 4 hours after RF ablation demonstrated necrosis of the TD wall and hemorrhage within the lumen. Histology at 14 and 30 days revealed fibrosis with hemosiderin-laden macrophages replacing the ablated TD. Collagen degeneration within the aortic wall involving a maximum of 60% thickness was noted in 5 of the 6 subjects.Percutaneous RF ablation can achieve short-segment TD occlusion. Further study is needed to improve safety and demonstrate clinical efficacy in treating TD leaks.

Giant cell tumors of soft tissue (GCT-ST) are rare low-grade neoplasms that were at one time thought to represent the soft tissue counterparts of GCT of bone (GCT-B) but are now known to lack the H3F3 mutations characteristic of osseous GCT. We present six distinctive giant cell-rich soft tissue neoplasms that expressed keratins and carried a recurrent HMGA2-NCOR2 gene fusion. Patients were five females and one male aged 14–60 years (median, 29). All presented with superficial (subcutaneous) masses that were removed by conservative marginal (3) or wide (2) local excision. The tumors originated in the upper extremity (2), lower extremity (2), head/neck (1), and trunk (1). Five patients with follow-up (median, 21 months; range, 14–168) remained disease-free. Grossly, all tumors were well-demarcated but not encapsulated with variable lobulation. Histologically, they were composed of bland plump epithelioid or ovoid to spindled mononuclear cells admixed with evenly distributed multinucleated osteoclast-type giant cells. Foci of stromal hemorrhage and hemosiderin were seen in all cases. The mitotic activity ranged from 2 to 14/10 high power fields (median: 10). Foci of necrosis and vascular invasion were seen in one case each. The mononuclear cells were immunoreactive with the AE1/AE3 keratin cocktail and less frequently/less diffusely for K7 and K19 but lacked expression of other lineage-associated markers. RNA-based next-generation sequencing revealed an HMGA2-NCOR2 fusion in all tumors. None of the keratin-negative conventional GCT-ST showed the HMGA2-NCOR2 fusion (0/7). Metaplastic bone (4/9) and SATB2 expression (3/4) were frequent in keratin-negative conventional GCT-ST but were lacking in keratin-positive HMGA2-NCOR2 fusion-positive tumors. The distinctive immunophenotype and genotype of these tumors strongly suggest that they represent a discrete entity, differing from conventional GCT-ST and other osteoclast-rich morphologic mimics. Their natural history appears favorable, although a study of additional cases and longer follow-up are warranted.

Introduction Myxoinflammatory fibroblastic sarcoma (MIFS) is a rare low-grade sarcoma presenting as a slow-growing mass that occurs mainly in the distal extremities of adults. Relatively little is known about the cytopathology of MIFS. We evaluated cytologic characteristics of MIFS on fine-needle aspiration (FNA). Materials and methods A search was made of our cytopathology and surgical pathology databases for cases diagnosed as MIFS. FNA biopsy smears and cell-block were performed and examined using standard technique. Results Eight cases were retrieved from patients aged 22-90 years (mean, 56 years), and M:F ratio of 1:1. Six tumors (75%) were primary, and 2 (25%) locally recurrent. Distal lower limb was involved in all but one case (88%). One (13%) recurrent case was correctly diagnosed cytologically as MIFS; remaining single diagnoses were varied: myxofibrosarcoma, low-grade sarcoma, malignant neoplasm, myxoid neoplasm, atypical fibrohistiocytic neoplasm, atypical cells with chronic inflammation, and spindle cells with atypia. Among 7 cases with available cytologic slides for review, common features were spindle cells with variable atypia (100%), rare virocyte/Reed-Sternberg -like cells (86%), background mixed inflammation (71%), and variable myxoid stroma (57%). Pseudolipoblasts and multinucleated giant cells were rare. Hemosiderin and branching capillaries were largely absent. Immunohistochemistry was non-specific. Conclusion MIFS was accurately interpreted in only 13% of cases; remaining cases were diagnosed as atypical or malignant, which would lead to proper management. A specific cytologic diagnosis of MIFS using FNA is extremely difficult in our experience due to an absence of distinctive cytomorphology and specific immunophenotype.

Purpose We report prospective clinical investigations of children affected with periodontal Ehlers-Danlos syndrome (pEDS). The main clinical features of pEDS in adults are early severe periodontitis, generalized lack of attached gingiva, and pretibial hemosiderin plaques due to dominant pathogenic variants in the C1R or C1S genes. Methods Nineteen children with a parent diagnosed with molecularly confirmed pEDS underwent physical examination including oral and radiological investigations followed by genetic testing. Results The only consistent manifestation of pEDS in childhood was a characteristic gingival phenotype: generalized lack of attached gingiva. All children with this gingival phenotype had inherited the familial pathogenic variant (n = 12) whereas the gingival phenotype was absent in children without the familial pathogenic variant (n = 7). Easy bruising was reported in eight affected and zero unaffected children. Other manifestations of pEDS were rarely present in children. Only 2/12 affected children aged 8 and 13 years fulfilled the clinical criteria for pEDS. Conclusion Generalized lack of attached gingiva is a pathognomonic feature of pEDS and the only clinical finding that is consistently present in affected adults and children. This is important because an early diagnosis may facilitate better dental hygiene in childhood, which may be essential to prevent early dental loss.

Chronic abruption oligohydramnios sequence (CAOS) is histologically characterized by diffuse chorioamniotic hemosiderosis (DCH). However, the criteria for the histological evaluation of the extent of CAOS-related hemosiderin deposition (HD) of the membranes and the difference in HD between the chorionic plate (CP) and fetal membrane (FM) are not well studied. This case control study compared the degree and distribution pattern of HD on CP and FM to present the histological features of DCH and the criteria for histological evaluation.From the medical records of Kyoto University Hospital (2010-2019), we selected 20 CAOS cases that were clinically diagnosed by Elliot's criteria. Twenty non-CAOS cases matched to the CAOS group by gestational age were selected as controls. We compared the clinical data and pathological features in the two groups. We performed iron staining in all the cases and analyzed HD in CP and FM according to the histological score (H-Score: 0-12), which was determined as the density (0-3) multiplied by the extent of staining (0-4).HD was found in 100% (20/20) of CAOS and 15% (3/20) of control cases. In both the FM and CP, CAOS cases showed a significantly higher HS than control cases (CAOS, HS = 4-12; Control, HS = 0-1, p 0.0001). Three CAOS patients presented HD alone in the CP. The HS of the CP was significantly higher than that of the FM (p = 0.0003).CAOS presented DCH with HS ≥ 4. This study showed that the CP might be more suitable for evaluating DCH than the FM.

Introduction Oil Red O (ORO) staining on cytologic specimens with calculation of the lipid-laden macrophage index (LLMI) is used as a part of the workup in a number of clinical settings, particularly when aspiration is of concern. As a part of ongoing internal quality improvement measures, the objective of the present study was to evaluate the interobserver agreement of the LLMI calculation and to identify factors that affect the variability of the calculation. Materials and methods There were 9 study participants, which included 3 trainees, 3 cytotechnologists, and 3 cytopathologists. Each participant reviewed 100 ORO-stained bronchoalveolar lavage slides and assigned an LLMI score to each case. The scores were categorized into 3 groups according to the associated aspiration risk: low, LLMI 90. The participants were also requested to note any challenges to the calculation for each case. Results The interobserver agreement among all participants was fair (κ = 0.23). Stratified by participant group, the interobserver agreement among the trainees was fair (κ = 0.24), among cytotechnologists was fair (κ = 0.32), and among cytopathologists was moderate (κ = 0.60). In 70 cases, at least one participant scored the case at least one category higher than the other participants; in 47 cases there was a two category difference. A primary diagnostic challenge reported by participants was macrophage pigmentation (hemosiderin, anthracosis). Conclusions We found only fair interobserver agreement among all 9 participants in the study. Hemosiderin and anthracotic pigmentation was a major factor impeding LLMI calculation resulting in overestimation of the LLMI.

Background Stereotactic radiosurgery (SRS) as a treatment for cerebral cavernous malformation (CCM) has been controversial, but there are few pathological reports showing its long-term therapeutic effect, and literature reporting the CCM cyst formation after SRS is also rare. Case Description We present a 30-year-old woman with a ruptured right parietal CCM treated with SRS 13 years ago. The post-SRS imaging follow-up revealed CCM rehemorrhage and cyst formation. Surgical resection was performed, and a subsequent pathological examination revealed that the CCM still had some incomplete occluded vessels and a large number of newly formed capillaries, and hemorrhagic band and hemosiderin were seen around the nodule. Conclusions Recurrent hemorrhage after SRS for CCM could be related to incomplete occluded vessels and newly formed capillaries. Repeated hemorrhage from CCM newly formed capillaries into the small cavity increased the osmotic pressure, resulting in fluid entering the cavity and cyst enlargement.

Intracranial hemorrhagic metastases are a relatively common finding in patients with thyroid carcinoma. Consequently, more unusual vascular lesions may be overlooked in contemplating a differential diagnosis in this patient group. A 50-year-old female with previously treated papillary thyroid carcinoma presented to the emergency department following new onset seizures. Her work up revealed multiple intraparenchymal brain lesions, hyperdense on computed tomography and demonstrating susceptibility effect, T1 shortening and contrast enhancement on magnetic resonance imaging, suggestive of metastases. Subsequent studies revealed lesional architecture consistent with multiple cavernous malformations, made evident by resolution of edema and evolution of blood products. Clinicians should be aware of the possibility of unusual intracranial hemorrhagic lesions in oncology patients which may only become evident on serial imaging evaluation. Cavernous hemangioma has typical MRI characteristic features which includes “mulberry” appearance on T2-weighted and fluid attenuation inversion recovery images with varying internal signal intensity which indicates multiple stages of blood products within the cavernous hemangioma. The lesions commonly have a typical T2-weighted dark hemosiderin rim. Blood sensitive demonstrates prominent surrounding hypointensity representing blooming secondary to internal blood products and/or calcification, if present. Cavernous hemangioma may rarely demonstrate some degree of contrast enhancement. Perfusion imaging may show alteration in capillary permeability involving cavernous malformations which has been previously described in the literature.

PubMed: 32376377 Background: Cerebral cavernomas are vascular malformations characterized by networks of abnormally dilated capillaries. They typically present as nodules with mixed signal intensity and a surrounding hemosiderin rim on magnetic resonance imaging. They may occur as multiple lesions in the autosomal-dominant familial form. In rare cases, cavernomas may form cystic masses, mimicking other pathologies. Case Description: A 35-year-old man presented with recurrent seizures, aphasia, and gait disturbance with onset at age 14 years. He had previously undergone surgical drainage of multiple cysts across the brain with suspected parasitic infection. On magnetic resonance imaging, 22 cystic lesions were seen across the brain. A large cyst was located in the midline cerebellum, compressing the fourth ventricle. Occipital craniotomy and transvermian dissection allowed total resection of the cyst along with its wall. The postoperative course was uneventful and symptoms progressively improved. Histological analysis revealed cavernoma. Three more surgeries were performed for removal of large supratentorial cavernomas. Conclusions: In patients with cystic lesions of the brain, the neurosurgeon should consider the possibility of cavernoma. Total excision along with the cyst wall is crucial for timely diagnosis and therapy. © 2020 Elsevier Inc.

The clinical impact of 5-aminolevulinic acid (5-ALA) fluorescence during resection of brain metastases is not yet clear.. Recent data demonstrated significantly lower incidence of visible fluorescence in cerebral melanoma metastases (CMM) compared to other brain metastases (BM). The aim of this study was to investigate if characteristic melanoma features such as pigmentation, intratumoural hemosiderin and bleeding have an influence on visible fluorescence in CMM.A retrospective study of two neurosurgical centers was performed including adult patients with resection of CMM after preoperative administration of 5-ALA. Data on the fluorescence status (visible or no fluorescence), the fluorescence quality (strong, vague, none) and fluorescence homogeneity (homogeneous or heterogeneous) of each CMM were collected. The amount of melanin, hemosiderin and intratumoural bleeding was semi-quantitatively determined and automated computer-based calculation of the relative pigmented area was performed in fluorescing and non-fluorescing CMM samples.Altogether, 29 CMM were surgically removed after 5-ALA administration. Visible fluorescence was detected in 8 CMM (28%), whereas no fluorescence was detected in 21 CMM (72%). In detail, 3 tumors (10%) showed strong fluorescence, 5 tumors (17%) revealed vague fluorescence and in 21 tumors (72%) no fluorescence was found. In total, 8 fluorescing and 25 non-fluorescing CMM samples were investigated. According to the semi-quantitatively calculated fluorescence status, no statistically significant difference in the median amount of melanin (p = 0.242), hemosiderin (p = 0.603) and bleeding (p = 0.762) between CMM samples with and without visible fluorescence was found. Moreover, the automatically assessed relative pigmented area did not show a statistically significant difference between samples with visible and no fluorescence (p = 0.966).Our data indicate that 5-ALA fluorescence is not dependent on the amount of pigmentation, intratumoural hemosiderin and bleeding in CMM. We thus assume that other factors are responsible for the low rate of visible fluorescence in CMM.

A 3-month-old first of dizygotic male twins, born at 34 + 5 weeks gestational age, presented with a 4-week history of increasing head circumference and vomiting. He had a tense anterior fontanelle and a head circumference above the 97th percentile. Magnetic resonance imaging showed large bilateral subdural collection with hemosiderin deposits suggestive of hemorrhage. Nine days of bilateral subdural drainage reduced the collection size and blood load. On postoperative day 16, magnetic resonance imaging confirmed persistent but smaller subdural collections, unmasking the underlying subarachnoid space enlargement. On day 18, a right subdural-peritoneal valveless shunt was inserted as definitive treatment. As part of a nonaccidental injury investigation, Twin 2 was also found to have macrocephaly secondary to benign enlargement of subarachnoid space, which was managed conservatively. Benign enlargement of subarachnoid space has an assumed autosomal/multifactorial inheritance and predisposes to subdural hemorrhage. Ultimately, no safeguarding issues were raised. Both twins continued to be neurologically stable at 2-year follow-up with head circumferences between the 98th and 99th percentiles.

In the porcine industry, some piglets show slightly enlarged and bluish inguinal lymph nodes. However, the causative factors for these signs and prevention of these signs remain unclear. Tylvalosin is a broad-spectrum antibiotic with an immunomodulatory function. This study was aimed at evaluating the effect of tylvalosin on the abovementioned signs. Thus, fifteen 90-day pregnant sows were divided into an untreated control group and 0.1 and 0.2 g/kg feed tylvalosin-treated groups until delivery. Forty-five piglets on day 2 after birth (15 each group) were blooded, then oxidative stress, serum cytokine levels, routine blood analysis, and effect of sera on macrophage phagocytic activity were examined. Fifteen piglets on day 2 after birth (5 in each group) were euthanized and pathological changes in the inguinal lymph nodes were observed. The untreated piglets showed hemorrhage, hemosiderin accumulation, and increased macrophages in the inguinal lymph nodes. However, tylvalosin administration in sows alleviated these signs in their piglets; increased total antioxidant capacity and serum glutathione levels; decreased serum IL-1β, TNF-α, and IL-10 levels; improved the percentages of neutrophils and lymphocytes in the blood; and increased the body weight of the weaning piglets. In addition, the serum of newborn piglets also showed enhanced RAW264.7 macrophage phagocytic activity. These results demonstrated that tylvalosin administration in pregnant sows attenuates the enlargement and bluish coloration of inguinal lymph nodes in newborn piglets.

Case A fit and well 25-year-old man presented with worsening pain and bony swelling on the lingual aspect of the right premolar region. Radiology showed a multiloculated radiolucent lesion of the anterior mandible with bone expansion and displacement of roots. Initial biopsy revealed fragments of nested epithelioid tumor within the marrow space with extravasated red blood cells and hemosiderin suggestive of vascular origin. Further biopsy showed histologic features of epithelioid haemangioendothelioma (eHAE). Samples were sent to the National Orthopaedic Hospital for molecular testing but this was inconclusive, likely owing to formic acid decalcification. MDT decision for surgical resection was carried out with primary reconstruction. Histology from the resection revealed complete excision of eHAE with focal erosion through the buccal cortex. The patient has recovered well, and to date there is no evidence of recurrence. Discussion eHAE is a very rare vascular tumor of low-grade malignancy, which presents within the lung, liver, or bone including of the head and neck region with 4 cases reported within the mandible. Despite characteristic morphology, diagnosis can be challenging because of small sample size and the rarity of diagnosis. eHAEs are characterized by a WWTR1-CAMTA1 fusion with a minority also showing a YAP1-TFE3 fusion, however decalcification in formic acid can prevent adequate molecular analysis. Conclusions eHAE is a rare tumor with characteristic histologic features and potential for recurrence and metastasis. Molecular testing can assist diagnosis, and development of local tissue pathways for intraosseous tumors that facilitate molecular testing is essential for prompt diagnosis.

Although the respiratory and immune systems are the major targets of Coronavirus Disease 2019 (COVID-19), acute kidney injury and proteinuria have also been observed. Currently, detailed pathologic examination of kidney damage in critically ill patients with COVID-19 has been lacking. To help define this we analyzed kidney abnormalities in 26 autopsies of patients with COVID-19 by light microscopy, ultrastructural observation and immunostaining. Patients were on average 69 years (19 male and 7 female) with respiratory failure associated with multiple organ dysfunction syndrome as the cause of death. Nine of the 26 showed clinical signs of kidney injury that included increased serum creatinine and/or new-onset proteinuria. By light microscopy, diffuse proximal tubule injury with the loss of brush border, non-isometric vacuolar degeneration, and even frank necrosis was observed. Occasional hemosiderin granules and pigmented casts were identified. There were prominent erythrocyte aggregates obstructing the lumen of capillaries without platelet or fibrinoid material. Evidence of vasculitis, interstitial inflammation or hemorrhage was absent. Electron microscopic examination showed clusters of coronavirus-like particles with distinctive spikes in the tubular epithelium and podocytes. Furthermore, the receptor of SARS-CoV-2, ACE2 was found to be upregulated in patients with COVID-19, and immunostaining with SARS-CoV nucleoprotein antibody was positive in tubules. In addition to the direct virulence of SARS-CoV-2, factors contributing to acute kidney injury included systemic hypoxia, abnormal coagulation, and possible drug or hyperventilation-relevant rhabdomyolysis. Thus, our studies provide direct evidence of the invasion of SARSCoV-2 into kidney tissue. These findings will greatly add to the current understanding of SARS-CoV-2 infection.

Background Superficial siderosis of the central nervous system is a rare neurologic disorder characterized by the superficial deposition of hemosiderin in the subpial layer resulting in iron-related progressive neurodegeneration. Case Description In this report, we present a case of superficial siderosis of the central nervous system secondary to an intradural thoracic disk herniation causing a cerebrospinal fluid (CSF) leak. Conclusions The patient was successfully treated with T6-T8 transpedicular partial corpectomy, as well as diskectomy with decompression followed by watertight closure of the CSF leak. Intraoperative watertight closure of the CSF leak was achieved.

Atrazine is a herbicide that is banned in Europe but remains widely used on different types of crops in several countries in the American continent. Atrazine is known to be an endocrine disruptor and its effects on gonads have been extensively reported, but the toxic action on other organs is poorly documented. In this paper, we investigated the toxicity of atrazine on the gills and spleens of Nile tilapia (Oreochromis niloticus). The median lethal concentration (LC50), capable of killing one-half of the test animals was calculated, and sublethal concentrations of atrazine were used in a semistatic and subchronic assay. The following four experimental groups were formed: control not exposed to atrazine, a group exposed to 1 ppm atrazine for 15 days, a group exposed to 2 ppm for 7 days, and a group exposed to 2 ppm for 15 days. The concentrations were verified during the study by high performance liquid chromatography. The gills and spleens were stained with hematoxylin and eosin and histopathological findings were made. The Perls technique was used on the spleens to identify hemosiderin, lipofuscin, and melanin pigments in the cells from melanomacrophage centres (MMCs). The spleens were submitted to proliferating cell nuclear antigen (PCNA) and inducible nitric oxide synthase (iNOS) immunohistochemistry, and morphometry was used to assess splenocyte proliferation and melanomacrophage iNOS expression. Finally, a colorimetric assay for caspase-3 was performed on the spleens to identify apoptosis. Vascular and structural alterations, such as venous sinus congestion, aneurysm, hemorrhage, pillar cell hypertrophy, disarrangement of secondary lamellae, and epithelial lifting were observed in the gills. The frequency of individuals with aneurysms was higher in the groups treated with 2 ppm than in other groups. Atrazine had an immunomodulatory effect on the spleen, observed by the alteration in the percentage of red and white pulp, alteration of the MMC area, changes in the melanomacrophage pigment content, slight iNOS suppression, decrease in splenocyte proliferation under 1 ppm atrazine, and increased caspase 3 activity under 2 ppm atrazine after 7 and 15 d. Such effects could compromise oxygenation and the immune response and, ultimately, the survival and fitness of the fish.

Background Klippel-Trenaunay-Weber syndrome (KTWS) is a rare congenital vascular disorder characterized by the classic triad of cutaneous nevi, venous varicosities, and osseous and soft tissue hypertrophy of the affected limb. Various vascular anomalies of the central nervous system have also been described in patients with KTWS. The English language literature to date contains 6 reports of associations between KTWS and spinal cord cavernous angioma (CA), but management of these patients has not been well described. Case Description A 23-year-old woman was admitted to our institution with acute onset of leg weakness accompanied by upper back pain. Thoracic magnetic resonance imaging of the spinal cord showed a heterogeneous mass with a slit component at the T1-2 level. The patient underwent left hemilaminectomy followed by removal of the tumor, and her neurologic symptoms improved postoperatively. Pathologic examination showed the spinal lesion was characterized by hemosiderin deposition and thin-walled vascular channels surrounded by fibrous tissue. Conclusions This is the first report to provide a detailed pathologic description of the features of spinal CA in a patient with KTWS. Assessment of the clinical features and management of CA associated with KTWS are discussed. This syndrome is rare, and further experience in the treatment of these patients is needed. However, considering that the pathologic findings of spinal CA in patients with KTWS include the typical features of CA, the management of CA in patients with KTWS may be identical to management of isolated CA.

Purpose Cerebral cavernous malformations are common central nervous system vascular malformations. They are typically a discrete, well-circumscribed cluster of thin-walled vascular sinusoids with a characteristic “mulberry” or “popcorn” appearance on magnetic resonance imaging and are often surrounded by hemosiderin deposits and gliosis. These malformations can present in a variety of ways. The purpose of this paper is to demonstrate presentations of cavernous malformations through cases with associated imaging. Materials/Methods 14 cases of cerebral cavernous malformations were retrospectively selected from a single institution from 2009 to 2019. The cases include classically appearing lesions as well as association with developmental venous anomaly and capillary telangiectasia. Results Variations included are large partially calcified lesions, hemorrhagic lesions, atypically shaped lesions, and lesions lacking the “popcorn” appearance or hemosiderin rim. Also presented is a case with multiple lesions and cases displaying the widespread locations of lesions. Locations include the cerebrum, cerebellar vermis, medulla, periaqueductal midbrain, spinal cord, and extradural intracranial cavernous sinus. Conclusion These cases and literature review illustrate how cerebral cavernous malformations can present. While often asymptomatic, the lesions can cause hemorrhage, seizures, and neurological deficits. They can present in atypical ways or masquerade as non-vascular lesions making diagnosis a difficult task.

Introduction Multiple subpial transection (MST) has been applied to the treatment of refractory epilepsy when epileptogenic zone involves eloquent areas since 1989. However, there is a lack of data evaluating the effect of this surgical technique on the cortex as measured by Magnetic Resonance Imaging (MRI). Patients and methods Ten consecutive patients (3F/7 M, average age: 18.5 years) were operated on using radiating MST (average: 39; min: 19, max: 61) alone (n = 3) or associated with another technique (n = 7). Seven patients underwent a post-operative 3.0 T MRI while 3 had a 1.5 T MRI. Three patients had an early post-operative MRI and 7 a late MRI, among which 3 previously had an intraoperative MRI. Results The MR sequences that allowed the best assessment of MST-induced changes were T2 and T2*. The traces of MST are more visible on late MRI. These discrete non-complicated stigmas of MST were observed in all 10 studied patients: on the intraoperative MRI they are seen as micro-hemorrhagic spots (hypo-T2), on the early postoperative MRI as a discreet and limited cortical edema whether associated or not with micro-hemorrhagic spots and on the late MRI as liquid micro-cavities (hyper-T2) surrounded with a fine border of hemosiderin. Conclusions MST-induced cerebral lesions are best visualized in T2-sequences, mainly on the late postoperatively MRIs. On all the MRI examinations in this study, the MST are only associated with limited modifications of the treated cortical regions.

Since the early 1980s, populations of American (Anguilla rostrata) and European eels (Anguilla anguilla) have suffered a sharp decline. The causes of their decline are likely multifactorial and include chemical pollution. A field study was conducted in eight sites varying in organic and metal contamination along the St. Lawrence (Eastern Canada) and Gironde (France) systems to investigate the relationships among contaminants, biological characteristics and biotransformation, antioxidant and histopathological biomarkers in eels from both species. For A. rostrata, no major influences of persistent organic contaminants on biomarkers were identified. For A. anguilla, eels from the most contaminated site expressed higher surface of MelanoMacrophage Centers (MMCs) and eels from another contaminated site expressed higher amount of spleen lipofuscin pigment. These two histopathological biomarkers were also associated with aging. Compared to eels from the cleanest French site, higher hepatic catalase activity and density of MMC in eels from contaminated sites was related to higher concentration of organic (DDT and metabolites, sum of PCBs, sum of PBDEs) and inorganic (Hg and Cd) contaminants. In both species, a higher deposition of spleen hemosiderin pigment was measured in eels from the most brackish sites compared to eels living in freshwater environments. Our results suggest an association between higher hemosiderin pigment and metal contamination (As for A. anguilla and Pb for A. rostrata). Parasitism by A. crassus was observed in European eels from freshwater sites but not in eels from brackish habitats. Overall, contamination may pose a greater risk for the health of European compared to American eels.

Background This study examined the structural outcomes for joints of boys with severe hemophilia A receiving frequency/dose‐escalated primary prophylaxis using magnetic resonance imaging (MRI), and the importance of interval MRI changes. Methods Forty‐six subjects (27 with interval studies) were evaluated by radiographs (X‐rays) and mid‐ and end‐of‐study MRIs (using the International Prophylaxis Study Group scale), as part of the Canadian Hemophilia Prophylaxis Study. The primary outcome was the presence of MRI osteochondral findings. Results The median (range) time on study at the end‐of‐study MRI examination was 9.6 (4.8–16.0) years, during which 18 of 46 subjects (39%) had osteochondral changes in at least one joint. An interval change in MRI score of at least 1 point was observed in 44% of joints (43 ankles, 21 elbows, 4 knees); at least one joint showed this change in all 27 subjects. Self‐reported interval hemarthrosis was associated with a higher likelihood of interval osteochondral change (odds ratio [OR], 1.49; 95% confidence interval [CI] = 1.08–2.06). Presence of synovial hypertrophy or hemosiderin on interval MRIs was associated with an OR of 4.71 (95% CI, 1.92–11.57) and 5.25 (95% CI, 2.05–13.40) of later osteochondral changes on MRI. Discussion MRI changes were seen in 39% of subjects. Interval index joint bleeding was associated with an increased risk of later MRI changes, and earlier soft‐tissue changes were associated with subsequent osteochondral changes.

Objective Patients with cavernous angioma (CA) often suffer from severe epilepsy, and surgical resection is often performed to attenuate these epileptic seizures. Several studies have suggested that surgical removal of the surrounding hemosiderin-pigmented tissues adjacent to CA achieves better seizure control than restricted lesionectomy. Pathological examination of the resected foci reveals not only hemosiderin pigmentation but also various degrees of inflammatory change, such as hemosiderin-laden macrophages, gliosis and fibrosis. However, there is some controversy regarding the epileptogenic potential of these regions due to the uncertain nature of the mechanisms contributing to these histopathological changes. Methods To investigate the correlations between neuron hyperexcitability and evident pathological changes, we performed ex vivo flavoprotein fluorescence imaging using surgically resected epileptogenic foci surrounding CA. The mirror surfaces of the tissues used for the physiological experiment were also subjected to morphological examination. Results Hemosiderin-laden macrophages and many gemistocytic astrocytes were observed in the area adjacent to CA, where horizontal spreading excitations were detected significantly more frequently. Outside these areas, we found fine granular iron deposits and only a few fibrillary astrocytes, and weakly propagating excitations were detected. Furthermore, areas of enhanced activation were more clearly correlated with the glial proliferation index than with iron deposition. Conclusion These results suggest that the epileptogenesis in patients with CA may be based on a biological process, such as alteration of glial function, rather than direct chemical reactions involving iron deposition.

Objectives The purpose of this study was to determine whether intraoperative electrocorticography (ECoG) results and postoperative pathological findings are associated with long-term epileptic outcomes in patients with cerebral cavernous malformations (CCMs). Methods and materials To identify all consecutive patients with surgically treated CCM-related epilepsy (CRE) referred to our hospital, our prospectively maintained database of patients with CCM was reviewed (NCT03467295). For these patients, an ECoG-guided extended lesionectomy was performed, in which the CCM, surrounding hemosiderin, and detected epileptic foci were removed. Intraoperative ECoG results and postoperative pathological findings were documented in detail. Engel Class I was defined as a favorable outcome, while Engel Class II-IV was considered an unfavorable outcome. The patients were followed up for at least 2 years. The relationship between ECoG results, postoperative pathological findings, and epileptic outcomes was analyzed. Results A total of 522 patients with CCM were reviewed, and 85 patients with epileptic CCM were enrolled in this study. At the last clinical visit, 83.5 % of the patients experienced favorable postoperative outcomes. Multivariate analysis revealed that residual epileptic waves detected by intraoperative ECoG (OR 13.64; Cl 2.13–87.11; p = 0.006) and concomitant focal cortical dysplasia (FCD) (OR 11.37; Cl 1.63–79.27; p = 0.014) were independent factors significantly correlated with long-term epileptic outcomes. Most (61; 93.8 %) of the 65 patients with CRE without FCD achieved favorable outcomes. Conclusion Residual epileptiform discharges after excision and concomitant FCD may be associated with poorer long-term epileptic outcomes in patients with CRE. Close follow-up and strict administration of oral antiepileptic drugs may be needed for these patients.

Background Cerebral cavernous malformations (CCM) can cause intracerebral hemorrhage. The lesions themselves are frequently associated with perifocal hemosiderin deposits caused by repetitive microhemorrhages. Main indications for a surgical treatment are recurrent symptomatic hemorrhages or cavernoma-related epilepsy. After surgical resection, follow-up magnetic resonance imaging (MRI) is usually performed to confirm 1) the complete resection of the CCM and, especially in cases of cavernoma-related epilepsy, 2) the complete resection of the hemosiderin deposits. Methods This prospective study evaluates the value of early postoperative MRI (within 72 hours) regarding the detection of CCM or hemosiderin remnants compared with a standard 3–6 months postoperative MRI control in 61 CCM cases. Results Sensitivity of early postoperative MRI for CCM remnant detection was 66.67% (95% confidence interval [CI], 9.43%–99.16%), specificity was 76.74% (95% CI, 61.37%–88.24%), positive predictive value was 16.67% (95% CI, 2.09%–48.41%), and negative predictive value was 97.06% (95% CI, 84.67%–99.93%). Because of the high number of patients who could not be evaluated because of imaging artifacts, sensitivity and specificity analysis was not performed for early postoperative MRI using T2*/susceptibility-weighted imaging to assess hemosiderin remnants. Sensitivity of early postoperative MRI for hemosiderin remnant detection using T2-weighted sequences was 85.71% (95% CI, 63.66%–96.95%), specificity was 66.67% (95% CI, 44.68%–84.37%), positive predictive value was 69.23% (95% CI, 55.45%–80.27%), and negative predictive value was 84.21% (95% CI, 64.31%–94.04%). Conclusions Our data suggest that early postoperative MRI after CCM surgery is often hampered by imaging artifacts creating false-positive results and therefore ineligible for a resection control. However, reliability of a negative result on early postoperative T2-weighted MRI is relatively high regarding both CCM and hemosiderin remnants.

The idiopathic bone cavity (IBC) is an intraosseous pseudocyst devoid of epithelial lining. Clinically, IBCs of the jaw are asymptomatic and normally found in routine radiographic exams. Although the literature regarding the content of IBCs is controversial, the final diagnosis is usually aided by the discovery of an empty cavity upon surgical exploration. The aim of this study was to perform cytological and histological analysis of IBC contents. Cytological analysis of nine cases of IBC was performed after puncture and processed by the cell block technique. Histological analysis was performed in six cases in which it was possible to collect enough material by curettage of bone walls. Remarkably, cell block analysis revealed the presence of fibrin, often arranged as a net; erythrocytes; and inflammatory cells, with a predominance of lymphocytes as well as some macrophages and neutrophils. Histological analysis showed the presence of scant connective tissue, bone trabeculae, hemorrhagic foci, and hemosiderin. Only two cases presented scattered multinucleated giant cells. Cytological evaluation of IBC content by the cell block technique might represent a useful diagnostic tool, especially in cases in which there is no available material for curettage in the cavity.

A survey to determine the pathogenic bacterial strains of an important commercial capture fish, Oreochromis niloticus in an Egyptian fish farm was conducted. One strain presumptively identified as Shewanella putrefaciens was isolated from the fish and identified by a biochemical test, API20NE system and 16S rRNA gene. Intraperitoneal (I.P) challenge by S. putrefaciens revealed its pathogenicity with 50% mortality. The infected fish showed skin hemorrhage, fin rot and shallow necrotizing ulcers on the skin with congestion and enlargement of the liver, spleen and kidneys. The antibiogram of S. putrefaciens revealed its sensitivity to ciprofloxacin, norfloxacin, nalidixic acid, streptomycin, gentamycin, oxytetracyclin and sulfamethoxazole. Complete resistance to cephazolin and fusidic acid was recorded. Histological changes in the liver of infected O. niloticus included hepatocyte degeneration, fatty vacuolation in liver cells, Kupffer cell increase, hemolysis with infiltration in blood vessels, deposition of hemosiderin associated with the liver blood vessels and necrosis hepatocytes in the fatty liver tissue. The results concluded that the S. putrefaciens should be considered as an opportunistic pathogen for fish, which had caused fish infections, diseases with septicemia and mortality in O. niloticus.

Buccal mucosa color is explained by hemoglobin in the vessels and melanin in the epithelium. Abnormal presence of melanin pigments (hypermelaninosis, hypermelanocytosis), hematic pigments (hemoglobin, hemosiderin, iron) but also some exogenous circonstancies explain pigmented lesions (figure 1). These lesions could be localized (single lesions), multifocal (multiple lesions) or diffused. In case of a localized pigmentation with melanic appearance, melanoma must be systematically eliminated with a biopsy. In the case of a more diffused lesion, systemic disease must be evoked. A drug etiology is also possible. A blood pigment excess could be a vascular malformation (flat lesions) or a tumoral process (nodular or swollen lesions). In both cases, Kaposi's disease should be systematically eliminated. Pigmentations near dental restorations (amalgams, prosthetic crowns) could be explained by an exogenous factor but a biopsy should be performed in case of a doubt with melanoma.

Iron, particularly hemosiderin, is a commonly observed pigment in cytology. Many pigments appear green to blue to black, making differentiation of pigment types difficult. While cytologic clues such as erythrophagia can help determine whether pigment is iron, Perl's Prussian Blue stain is used to highlight iron when these clues are not present. Other special stains can identify similar pigments such as copper. Identification of pigments is important as it directs cytologic interpretation, thus directly influencing patient diagnosis. This paper also presents basic iron metabolism, iron disorders in small animals, and laboratory assessment of iron disorders.

Background Hemophilic arthropathy is a severe complication of hemophilia. It is caused by recurrent bleeding into joint cavities, which leads to synovial inflammation, fibrosis, cartilage degradation, and bone remodeling. Extracellular matrix remodeling of affected tissues is a hallmark of these pathological processes. Objectives The aim of this study was to use serological biomarkers of collagen turnover to evaluate extracellular matrix remodeling in a factor VIII-deficient rat model of hemophilic arthropathy. Methods F8-/- rats and wild-type littermate controls were subjected to repeated knee bleeds induced by needle puncture on days 0 and 14. Development of arthropathy was confirmed by histology upon termination on day 28. Serum samples were collected at baseline and throughout the study, and analyzed for biomarkers of collagen turnover including collagens of the basement membrane (type IV collagen), the interstitial matrix (collagen types III, V, and VI), and cartilage (type II collagen). Results In F8-/- rats, induced knee bleeding and subsequent development of arthropathy caused significant alterations in collagen turnover from baseline to termination, measured as changes in serological biomarkers of basement membrane turnover, interstitial matrix turnover, and cartilage degradation. Biomarkers of type II collagen degradation correlated significantly to cartilage degradation and degree of arthropathy. Hemophilic rats had a 50% higher turnover of the basement membrane than wild-type littermates at baseline. Conclusions Joint bleeding and hemophilic arthropathy cause changes in turnover of extracellular matrix collagens in hemophilic rats. Biomarkers of collagen turnover may be used to monitor joint bleeding and development of blood-induced joint disease in hemophilia. This article is protected by copyright. All rights reserved.

Made available in DSpace on 2021-06-25T10:48:40Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-03-01 Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) British and Foreign School Society The liver of anurans play an important role in metabolism, including detoxification, the biotransformation of molecules, and the storage of metabolites. Surfactants are part of domestic and industrial effluents. The effects of linear alkylbenzene sulfonate (LAS) on anuran liver remain unknown, however, some studies have evaluated the effects of LAS on the skin, gills, heart, testes, and liver of fishes. Here, we tested the hypothesis that LAS is hepatotoxic, promoting morphometric alterations in hepatocytes along with inflammation in the tissue, altering hepatic catabolism. We evaluated the effects of a LAS concentration that is considered environmentally safe in Brazilian inland waters on the liver of Lithobates catesbeianus tadpoles, including studies on morphology, morphometry, immunology, and metabolism. LAS exposure promoted enlargement of liver sinusoids and vacuolization of hepatocytes. Exposure to LAS also increased the area of mast cells and melanomacrophages (MMs). Additionally, LAS exposure increased hemosiderin inside MMs, suggesting alterations in the catabolism and storage of iron. Hepatocyte size increased after exposure to LAS, suggesting cytotoxic effects. Integrative analyses (i.e., morphometric, metabolic, and immunological) demonstrated hepatotoxic effects of LAS. These types of studies are key to understanding the negative effects of these substances on tadpole health, as these liver alterations impair anuran homeostasis. Laboratório de Fisiologia da Conservação (LAFISC) Universidade Federal de São Carlos (UFSCar) Departamento de Biologia Universidade Estadual Paulista (UNESP), São José do Rio Preto Laboratório de Patologia Experimental (LAPEx) Instituto de Biociências (INBIO) Universidade Federal de Mato Grosso do Sul UFMS Laboratório de Ecotoxicologia e Biomarcadores Em Animais (LEBA) Universidade Federal de São Carlos, Sorocaba Laboratório de Biologia Estrutural e Funcional Universidade Federal de São Carlos, Sorocaba Laboratório de Microbiologia Ambiental (LAMA) Universidade Federal de São Carlos, Sorocaba RECETOX Faculty of Science Masaryk University, Kamenice 753/5, Pavilion A29 Departamento de Biologia Universidade Estadual Paulista (UNESP), São José do Rio Preto CNPq: #573921/2008–3 FAPESP: 08/57712–4 FAPESP: 2014/00946–4 British and Foreign School Society: 304552/2019–4 CNPq: 304552/2019–4 CNPq: 573921/2008–3

UNLABELLED Essentials Validating the F8 rat as a new intermediate-size animal model of hemophilic arthropathy. Factor VIII (FVIII) treated F8(-/-) rats suffered induced hemarthrosis analyzed by histopathology. F8 (-/-) animals develop hemophilic arthropathy upon hemarthrosis, preventable by FVIII treatment. The F8 (-/-) rat presents as a new pharmacologic model of hemophilic arthropathy. SUMMARY Background Translational animal models of hemophilia are valuable for determining the pathobiology of the disease and its co-morbidities (e.g. hemophilic arthropathy, HA). The biologic mechanisms behind the development of HA, a painful and debilitating condition, are not completely understood. We recently characterized a F8(-/-) rat, which could be a new preclinical model of HA. Objectives To establish the F8(-/-) rat as a model of HA by determining if the F8(-/-) rat develops HA resembling human HA after an induced joint bleed and whether a second joint bleed causes further disease progression. Methods Wild-type and F8(-/-) rats were treated with vehicle or recombinant human factor VIII (rhFVIII) prior to a needle-induced joint bleed. Joint swelling was measured prior to injury, the following 7 days and upon euthanasia. Histologic sections of the joint were stained, and athropathic changes identified and scored with regard to synovitis, bone remodelling, cartilage degradation and hemosiderin deposition. Results Vehicle-treated F8(-/-) rats experienced marked joint swelling and developed chronic degenerative joint changes (i.e. fibrosis of the subsynovial membrane, chondrocyte loss and excessive bone remodeling). Treatment with rhFVIII reduced or prevented swelling and degenerative joint changes, returning the F8(-/-) animals to a wild-type phenotype. Conclusion The hemophilic phenotype of the F8(-/-) rat resulted in a persistent hemarthrosis following an induced joint bleed. This caused development of HA resembling human HA, which was prevented by rhFVIII treatment, confirming the potential of the F8(-/-) rat as a model of HA.

A 15-year-old intact female sugar glider ( Petaurus breviceps ) presented for a 3-day history of diarrhea and weight loss despite an excellent appetite. Upon physical examination under manual restraint, the animal was determined to be emaciated with a palpable lcm diameter, firm, and irregular abdominal mass. Following 72 hours of supportive and palliative treatment (including oral antibiotics and glucocorticoids) with no clinical response, the owner elected euthanasia and approved antemortem diagnostics for teaching purposes. A complete blood count revealed a moderate regenerative anemia, mild leukopenia, and thrombocytopenia. A significant number of sideroleukocytes were noted upon examination of a blood smear, along with platelet clumps. Plasma biochemical analysis showed moderate hypoproteinemia, moderate hypoalbuminemia, mild hypokalemia, and elevated total bilirubin. Mild hypernatremia and hyperchloremia were also present. An abdominal ultrasound confirmed the presence of a large hypoechoic abdominal mass, which appeared to be associated with the liver. Whole-body radiographs did not assist in reaching an antemortem diagnosis because of poor abdominal serosal detail secondary to severe emaciation. Postmortem examination and histopathology provided a definitive diagnosis of concurrent hepatocellular carcinoma and adrenocortical carcinoma with no evidence of metastases. Hemosiderin pigment accumulation was noted within macrophages and hepatocytes.

Senna occidentalis (S. occidentalis) is a toxic leguminous plant that contaminates crops and has been shown to be toxic to several animal species. All parts of the plant are toxic, but most of the plant's toxicity is due to its seeds. Despite its toxicity, S. occidentalis is widely used for therapeutic purposes in humans. The aim of the present work was to investigate, for the first time, the effects of the chronic administration of S. occidentalis seeds on hematopoietic organs, including the bone marrow and spleen. Fifty male Wistar rats were divided into five groups of 10 animals. Rats were treated with diets containing 0% (control), 0.5% (So0.5), 1% (So1), or 2% (So2) S. occidentalis seeds for a period of 90 days. Food and water were provided ad libitum, except to pair-fed (PF) group which received the same amount of ration to those of So2 group, however free of S. occidentalis seeds. It was verified that rats treated with 2% S. occidentalis seeds presented changes in hematological parameters. The blood evaluation also showed a significant decrease of the Myeloid/Erythroid (M/E) ratio. Chronic treatment with S. occidentalis promoted a reduction in the cellularity of both the bone marrow and spleen. Additionally, we observed changes in bone marrow smears, iron stores and spleen hemosiderin accumulation. Histological analyses of bone marrow revealed erythroid hyperplasia which was consistent with the increased reticulocyte count. These findings suggest that the long-term administration of S. occidentalis seeds can promote blood toxicity.

Hepcidin, interleukin 1-β (IL-1β), and cytochrome P450 1A (CYP1A) genes play an important role in the adaptive immune system in fish. To our knowledge, this is the first observation among the expression level of these genes in response to infection with Aeromonas hydrophila and Pseudomonas fluorescens in Nile tilapia (Oreochromis niloticus). Also, the effect of these experimentally induced infections was investigated regarding the mortality rate, clinical signs, and histopathological changes in the liver and kidney tissues. Three experimental fish groups were injected intraperitoneally (IP) by 0.1 ml of phosphate-buffered saline, two of these groups were injected by 0.1 ml of 1 × 105 CFU/ml of the suspension of either A. hydrophila or P. fluorescens. The infected groups showed extensive skin hemorrhages, cloudiness of eyes, protrusion of the scales, and severe swelling of the abdomen with inflammation of the vent and the mortality rate (MR%) was 42.75 and 37.5% in A. hydrophila and P. fluorescens groups, respectively. The histological changes of the infected O. niloticus with A. hydrophila and P. fluorescens showed fibrosis, karyolitic necrosis, the disappearance of hepatocytes wall and deposits of hemosiderin in the liver, while kidney showed dilation in Bowman's spaces, disconnection of renal tubules and hemorrhage and necrotic areas between them besides the accumulation of hemosiderin. The relative expression levels of hepcidin were higher after A. hydrophila than P. fluorescens infection in most studied organs while other studied genes expression levels were varied between infected fish groups. The relative expression of hepcidin was increased in the liver, blood, pituitary, kidney, and ovary while IL-1β transcripts were increased in the liver, kidney, muscle, gill, brain, and blood. CYP1A transcripts were increased in the liver, kidney, gill, and testis. The magnitude of the increase in IL-1β levels differed from that observed for the hepcidin and CYP1A genes. The relative expression levels of studied genes were significantly increased in the liver followed by the kidney. No significant differences were observed in the relative expression of studied genes among the gill, blood, brain, and pituitary and among the ovary, testis, brain, and pituitary during the bacterial challenge (p

The giant cell central lesion (LCCG) is considered to be rare and benign, and its etiology is uncertain. Clinically and radiographically, it can be differentiated between aggressive and nonaggressive lesions. A female patient with leukoderma, 13 years old, presented with discrete asymmetry in the right hemiface and increased volume in the anterior region of the mandible, of indurated consistency, and painless palpation. In the imaging examinations, the presence of a radiolucent, multilocular, well-delimited image in the anterior region of the mandible crossing the midline, with tooth dislocation was observed. Histopathology revealed a loose, richly vascularized fibrous connective tissue fragment exhibiting intense proliferation of spindle and oval cells with large numbers of nonspecific multinucleated giant cells. Hemorrhagic areas and deposits of brownish pigmentation were compatible with hemosiderin. The diagnosis was central giant cell lesion. The conservative drug therapy was performed, which was not successful, and the surgical intervention was performed. Postoperative control is 6 months, without recurrence.

Awake craniotomy allows mapping of eloquent brain regions and monitoring neurocognitive functioning intraoperatively to maximize extent of resection and minimize cognitive morbidity.1,2 During resection of cavernous malformations in eloquent areas, intraoperative cognitive monitoring can also allow for safer maximal excision of the hemosiderin ring, which is correlated with improved seizure-free outcome.3,4 We present the case of a 33-year-old right-handed male with a new-onset seizure who presented to his local emergency department after experiencing visual hallucinations before losing consciousness. Computed tomography scan of the head revealed a calcified lesion in the left temporal/parietal area. Presurgical workup revealed left hemispheric language dominance and language activation within the overlying supramarginal gyrus representing phonologic working memory on functional magnetic resonance imaging.5 Diffusion tensor imaging identified the arcuate fasciculus and lateral portion of the superior longitudinal fasciculus to be intimately associated with the deep margin of the lesion.6 After consent was obtained, we performed an awake craniotomy and resection of the lesion through a transsulcal approach, with eloquent cortical mapping using a novel high-density circular grid,7,8 as well as subcortical stimulation/mapping and continuous intraoperative cognitive monitoring using multiple language paradigms; the patient was baselined on these paradigms preoperatively (Video 1). Several phonologic/paraphasic errors were made during resection of the hemosiderin ring, likely related to mechanical manipulation. The patient was discharged to home on postoperative day 4 with outpatient speech therapy for speech hesitancy. At 1-week postoperative testing, language skills were considered within normal limits.

Background Superficial siderosis is an irreversible disease in the central nervous system caused by the deposition of hemosiderin in the subpial tissue due to persistent bleeding in the subarachnoid space. The main symptoms include sensorineural hearing loss, cerebellar ataxia, and pyramidal tract disorder. Superficial siderosis is mainly idiopathic, but bleeding factors such as tumors or history of surgery often play an important role in its pathogenesis. Case Description A 66-year-old man with a history of surgery for a cerebellar tumor 37 years ago complained of hearing loss. Magnetic resonance imaging showed recurrence of the tumor on T2-weighted images and hypointense areas along the cerebellar sulci on T2∗-weighted images. During the operation, microscopic bleeding was observed on the surface of the tumor. The pathologic diagnosis was pilocytic astrocytoma. A biopsy obtained during the first surgery revealed almost the same pathologic findings as those from a biopsy obtained during the second surgery, but the first specimen showed no hemosiderin deposition or active bleeding, which the second specimen did show. Conclusions Recurrent pilocytic astrocytoma with intratumoral hemorrhage was the suspected cause for superficial siderosis. The source of chronic bleeding was identified with intraoperative and pathologic findings. We describe the first report of superficial siderosis associated with a pilocytic astrocytoma that recurred 37 years after an initial tumor was excised.

Copper is an essential micronutrient but its excess in the dietary can be toxic. Both copper deficiency and abundance can occur in natural conditions and can lead to pathological dysfunctions. Many of the toxic effects of copper, such as increased lipid peroxidation in cell membranes and DNA damage, are due to its role in the generation of oxygen free radicals. Copper is released into the environment by both natural sources and human activities and it can damage organisms and ecosystems. In the present work the effects of copper has been studied on Xenopus laevis, an interesting model organism, after three weeks of exposure at 1 mg/L of CuCl, concentration allowed in the water for human use. The effects of this metal were analysed on the liver at light microscope by Hematoxylin-Eosin, Mallory, Pas and Perls stainings to evaluate the general histology, the glycogen metabolism and presence of hemosiderin. Moreover the number and area of melanomoacrophages, known as inflammation parameters, were assessment. Finally, we investigated the expression of atp7b gene and localization of respective ATP7B protein, the membrane protein involved in Cu detoxication. The achieved results showed that copper, even at a low concentration, causes serious histological alterations of liver. It induces an increase in the size and number of melanomacrophages and higher amount of hemosiderin in the treated than controls. Moreover, it alters the gene expression and localization of ATP7B protein. The data are indicative that an exposition at low and chronic concentration of copper in Xenopus laevis damages seriously the liver. For this reason it's important to consider this metal one of the pollutants involved in the decline of the amphibians and for its possible effects in other vertebrates including humans.

Objectives This study sought to assess the accuracy of optical coherence tomography (OCT), gray-scale intravascular ultrasound (IVUS), and their combination for detecting thin-cap fibroatheromas (TCFA). Background The extent to which the imaging characteristics of OCT and IVUS correlate with histologically defined TCFA is unknown. Methods IVUS and OCT examinations identified focal plaques in 165 coronary arteries from 60 autopsy hearts. A total of 685 pairs of images of OCT and IVUS were compared with histology. By OCT, a TCFA was defined as a signal-poor region with diffuse borders and cap thickness Results With histology as the gold standard, the sensitivity, specificity, positive predictive value, negative predictive value, and overall diagnostic accuracy for OCT-derived TCFA were 100%, 97%, 41%, 100%, and 98%, respectively. The corresponding numbers for IVUS-derived TCFA were 92%, 93%, 19%, 99%, and 93%, respectively. The histological findings underlying the false positive diagnoses of OCT for TCFA included large amounts of foam cell accumulation on the luminal surface, large amounts of microcalcifications at the surface, large amounts of hemosiderin accumulation, or organized thrombus. In contrast, histological causes of mischaracterization of TCFA by IVUS were mostly TCFA. When both OCT and IVUS criteria for TCFA were required to be met, the sensitivity, specificity, positive predictive value, negative predictive value, and overall diagnostic accuracy were 92%, 99%, 69%, 99%, and 99%, respectively. Conclusions In the present study, neither OCT nor IVUS were optimal to detect TCFA. The combined use of OCT and IVUS may improve TCFA detection accuracy.

Intra-articular post-traumatic ankle joint mass is a rare entity that may mimic other pathologies, mainly localized form of pigmented villonodular synovitis (LPVS) regarding the clinical and imaging characteristics. We report the case of a 16-year-old female patient that presented an intra-articular ankle joint mass 8 months after an ankle joint sprain for which magnetic resonance imaging (MRI) suggested LPVS as possible diagnosis due to the presence of hemosiderin deposits. Diagnosis of a post-traumatic hematoma of her ankle joint was made via fine needle aspiration (FNA) biopsy and anterior ankle arthroscopy. At one-year-follow-up after the arthroscopic excision of the hematoma, the patient remained asymptomatic and pain free while MRI revealed no pathologic findings. This case demonstrates that LPVS is not always the diagnosis when hemosiderin deposits are depicted on the MRI of a solitary intra-articular mass. The FNA biopsy under direct arthroscopic view assists the diagnosis and guides the treatment plan in cases that no definite diagnosis has been reached preoperatively by MRI. Level of evidence IV, case report.

Kidney injury is a complication of intravascular hemolysis associated with many forms of hemolytic disease. Reports of kidney biopsy findings in patients with hemolysis-related kidney injury have focused primarily on the accumulation of hemosiderin pigment within proximal tubular epithelial cells (hemosiderosis), a feature of chronic hemolysis. The nephrotoxic effects of hemoglobin include direct cytotoxicity to tubular cells, but hemoglobin also can precipitate in distal nephron segments, forming obstructive casts. We present a case of hemolysis-associated tubular injury, characterized by acute onset of intravascular hemolysis followed by acute kidney injury with acute tubular injury and abundant intratubular casts containing hemoglobin.

Leukoencephalopathy with calcifications and cysts (LCC) is an uncommon condition of unknown etiology occurring in children and adults. Pathological findings include obliterative hyalinosis of the small vessels, myelin loss, intense gliosis, Rosenthal fiber formation, microcalcifications, and hemosiderin deposits. Herein we report a 55-year-old man with LCC documented 10 years ago, in whom we examined brain perfusion by pseudocontinuous arterial spin labeling technique. We demonstrated diffused hypoperfusion of the affected white matter (WM) and of the subcortical gray matter (GM) and cortical GM in the patient in comparison to a group of healthy control subjects, using both qualitative evaluation and region of interest analysis. WM and subcortical GM hypoperfusion reflects the known distribution of LCC microangiopathy. We speculate that cortical hypoperfusion may be related to cerebral atrophy or may reflect deafferentation secondary to severe leukoencephalopathy, and may possibly contribute to severe motor and cognitive impairment. Further studies addressing cerebral blood flow in LCC are necessary.

Microbleeds, small perivascular collections of hemosiderin manifested radiologically as hypointensities on gradient-echo magnetic resonance imaging (MRI), are important markers of small vessel pathology. Despite their clinical relevance, little is known about their prevalence and demographic correlates, particularly among ethnically diverse older adults. We examined demographic and clinical correlates of regional microbleeds in a multi-ethnic cohort and examined categorization schemes of microbleed distribution and severity.Between 2005 and 2007, 769 individuals participated in a MRI study as part of the Washington Heights/Inwood Columbia Aging Project. Approximately four years later, 243 out of 339 participants (mean age=84.50) who returned for a repeat MRI had gradient-echo scans for microbleed assessment and comprised the sample. We examined the association of deep and lobar microbleeds with age, sex, education, vascular factors, cognitive status and markers of small vessel disease.Sixty-seven of the 243 (27%) participants had at least one microbleed. Individuals with microbleeds were more likely to have a history of stroke than individuals without. When categorized as having either no microbleeds, microbleeds in deep regions only, in lobar regions only, and both deep and lobar microbleeds, hypertension, proportion of strokes, and white matter hyperintensity volume (WMH) increased monotonically across the four groups. The number of lobar microbleeds correlated with WMH volume and diastolic blood pressure.Microbleeds in deep and lobar locations are associated with worse outcomes than microbleeds in either location alone, although the presence of lobar microbleeds appears to be more clinically relevant.

Brain vascular malformations are relatively common lesions that cause serious neurologic disability or death in a significant proportion of individuals bearing them. The purpose of this study was to analyze the clinicopathologic and immunohistochemistry these lesions, looking for common antibodies expressed such as CD31, CD34, CD15, factor VIII, nestin, vimentin, vascular endothelial grow factor (VEGF), vascular endothelial grow factor receptor-2 (VEGF-R2), glial fibrillar acidic protien (GFAP), and fibroblastic grow factor β (β-FGF) and ultrastructure in endothelial cells as well as in vessel walls. Fifty cases of vascular lesions were included in this study: 29 (58%) of them were arteriovenous malformations and 21 (52%) were brain cavernomas. Twenty-six (52%) patients were women and 24 (48%) men. The age range was from 13 to 68 years (mean age, 35.86 ± 15.19 years). The size of the lesions ranged between 1 and 8 cm (3 ± 1.65 cm), and parieto-occipital lesions had a bigger size. Evolution time varied from 1 month to 1 year (mean, 7.5 months). There was a significant statistical correlation between age and sex (P = -035), rupture of lesion (P = .015), brain hemorrhage (P = .033), necrosis (P = .011), hemosiderin deposit (P = .042), VEGF (P = .015), and VEGFR (P = .037), as well as localization of rupture (P = .017), loss of consciousness (P = .000), visual deficit (P = .026), hyaline vessels (P = .000), and CD31 (.009). Interactions between endothelial cells and mural cells (pericytes and vascular smooth muscle cells) in blood vessel walls have recently come into focus as central processes in the regulation of vascular formation, stabilization, remodeling, and function in brain vascular lesions. However, the molecular mechanisms that underlie the formation and growth of brain arteriovenous malformations are still poorly understood.

Platelet Endothelial Cell Adhesion Molecule 1 (PECAM-1) deficient mice in the FVB/n strain exhibit fatal chronic pulmonary fibrotic disease. The illness occurs in the absence of a detectable pro-inflammatory event. PECAM-1 is vital to the stability of vascular permeability, leukocyte extravasation, clotting of platelets, and clearance of apoptotic cells. We show here that the spontaneous development of fibrotic disease in PECAM-1 deficient FVB/n mice is characterized by early loss of vascular integrity in pulmonary capillaries, resulting in spontaneous microbleeds. Hemosiderin-positive macrophages were found in interstitial spaces and bronchoalveolar lavage (BAL) fluid in relatively healthy animals. We also observed a gradually increasing presence of hemosiderin-positive macrophages and fibrin deposition in the advanced stages of disease, corresponding to the accumulation of collagen, IL-10 expression, and myofibroblasts expressing alpha smooth muscle actin (SMA). Together with the growing evidence that pulmonary microbleeds and coagulation play an active part in human pulmonary fibrosis, this data further supports our hypothesis that PECAM-1 expression is necessary for vascular barrier function control and regulation of homeostasis specifically, in the pulmonary environment.

Objective Cyst formation is a well-known complication following radiosurgery for arteriovenous malformations (AVMs). In this retrospective study, the authors studied predictors for AVMs using magnetic resonance imaging (MRI) to assess the mechanism of cyst formation after linac-based radiosurgery (LBRS). Methods From April 1993 to April 2008, LBRS was performed on 109 patients with cerebral AVMs at our institution. Six patients (5.5%) were diagnosed with cyst formation after LBRS, and 5 of them underwent regular MRI follow-up every 3–4 months for 2 years post-LBRS, and every 6–12 months thereafter. Results Time from initial LBRS until cyst formation ranged from 8 months to 10.5 years. MRI showed contrast changes at the irradiated site and its periphery within a period of 4 months to 7 years after the initial LBRS. Moreover, the emergence of a high-intensity area (HIA) was observed on T2-weighted MRI (T2W-MRI) during the same period when changes were found on contrast-enhanced imaging. The emergence of a low-intensity area on T2W-MRI was observed prior to cyst formation or expansion, which was believed to be due to a subclinical hemorrhage near the irradiated region in all patients. Histological examination of the cyst nodule revealed hemosiderin deposits and microbleeding. Conclusions Future cyst formation was suggested by the emergence of subclinical hemorrhage (microbleeding) in an irradiated field after gadolinium-enhanced MRI showed contrast changes and T2W-MRI showed a HIA around the irradiated field. MRI follow-up should be conducted on a regular basis in such patients, even after a complete occlusion has been diagnosed.

Background Anemia and relative iron deficiency (RID) are prevalent in patients with heart failure (HF). The etiology of anemia and RID in HF patients is unclear. Hepcidin expression may be closely related to anemia and RID in HF patients. Although hepcidin is produced mainly by the liver, and the most frequent histologic appearance of liver in HF patients is congestion, the influence of liver congestion (LC) on hepcidin production has not yet been investigated. We investigated whether hepcidin contributed to anemia and RID in rats with LC. Methods and Results LC was induced in rats by ligating the inferior vena cava and compared with bleeding anemia (BA) model induced by phlebotomy and hemolytic anemia (HA) model induced by injection of phenylhydrazine. BA and HA strongly suppressed expression of hepcidin in liver and so did not cause decrease in serum iron and transferrin saturation. However, hepcidin expression did not decrease in LC rats, which resulted in anemia and lower transferrin saturation. In addition, many cells with hemosiderin deposits were observed in the liver and spleen and not in the bone marrow, and this appeared to be related to suppression of hepcidin expression. Iron accumulated in hepatocytes, and bone morphogenetic protein 6, which induces hepcidin, increased. Inflammation was observed in the congestive liver, and there was an increase in interleukin-6, which also induced hepcidin and was induced by free heme and hemoglobin via Toll-like receptor 4. Conclusions We conclude that LC contributes to RID and anemia, and it does so via inappropriate expression of hepcidin.

Objective The objective of this study was to retrospectively review the postoperative seizure outcome in patients with short duration of epilepsy associated with cavernous malformations and analyze the effect of surgical methods on seizure outcome in such population. Methods 36 patients with short duration of epilepsy (shorter than 12 months) associated with cavernous malformations in temporal or frontal lobe underwent microsurgical resection. The patients were retrospectively divided into two groups: Group A (21 patients) with complete removal of hemosiderin rim and Group B (15 patients) with partial removal of hemosiderin rim. Clinical follow-up was achieved with telephone correspondence or outpatient assessment. The seizure outcome was based on Engel’s classification. Results After a mean follow-up period of 18 months, 77.8% of the patients (28/36) were classified into Engel class I, including 19 patients (90.5%) in the complete removal of hemosiderin rim group (Group A) and 9 patients (60%) in the partial removal of hemosiderin rim group (Group B). Seizure outcome was significantly better in Group A. There was no mortality and all the postoperative neurological deficits were recovered at the time of follow-up. Conclusion The analysis of the seizure outcome demonstrate patients with short duration of epilepsy associated with cavernous malformations could benefit greatly from complete resection of hemosiderin rim and cavernous malformations.

Introduction Susceptibility-weighted imaging offers information about any tissue that has a different susceptibility from its surrounding structures such as deoxygenated blood, hemosiderin, ferritin, and calcium. It can detect minute hemorrhages, old microbleeds as well as thrombosed veins or sinuses. Purpose The aim of this work was to evaluate the importance of susceptibility weighted imaging (SWI) in management of cerebro-vascular strokes. Patients and methods The study was conducted upon 50 patients presenting with cerebro-vascular strokes within 72 h after the onset of the neurological symptoms. All patients were subjected to non-contrast CT of the brain as well as MRI of the brain including susceptibility weighted MRI. Results Among the 50 studied patients, 46 had infarctions (92%), while three patients had hematomas (6%) and one patient (2%) had no infarctions or hematomas but transverse sinus thrombosis. Among the 46 infarctions CT detected hemorrhagic transformation in two patients (4.3%) while the SWI detected hemorrhagic transformation in ten patients (21.7%). Both the CT and SWI detected the hematomas in three patients. SWI detected old micro-bleeds in eight patients out of 50 (16%), while CT could not detect any of these micro-bleeds. These eight patients included four with non-hemorrhagic infarctions, three with hematomas and one with early hemorrhagic transformation. SWI detected sinus thrombosis in two cases out of 50 (4%), one had hemorrhagic infarction, and the other had no visible brain insults on CT. Management was planned for each group according to the presence or absence of hemorrhagic transformation of infarction or associated old microbleeds. Conclusions Susceptibility-weighted imaging is an important technique that allows accurate detection of early hemorrhagic transformations within acute infarctions as well as detecting old microbleeds thus alarming the treating physician about the devastating complication of anticoagulant therapies. Also SWI can early detect cerebral venous thrombosis. Thus SWI should be a routine sequence in the protocol of stroke imaging.